The cell mediated, immune, granulomatous host response to eggs deposited in the tissues is the major cause of pathology associated with schistosomiasis. An estimated 200,000,000 individuals are infected and manifest a wide range of clinical syndromes from asymptomatic to severe hepatosplenic disease; however, the factors which determine individual expression within the disease spectrum are not understood. The in vitro technology, developed in this laboratory, permits the analysis of the cell populations responsible for granuloma formation and its modulation. Previous studies have defined the contributing populations as macrophages, several subpopulations of lymphocytes, eosinophils, neutrophils and fibroblasts. These populations will be analyzed for their roles in initial antigenic recognition and responses, central intramodulation, participation in subsequent recruitment reactions, and fibrogenesis. A variety of functional, morphologic and antigenic criteria will be used to define, quantitate, and isolate these populations. They will then be utilized, in sequential recombination experiments, to analyze the pathways of cellular interaction which culminate in granuloma formation and fibrosis. The pathophysiologic consequences of these interactions will be assessed through subsequent in vivo transfer experiments. A recently developed modification of the in vitro granuloma techniques has permitted the utilization of more defined antigens, passively or covalently complexed in 60Mu latex beads. This methodology, which appears quite analogous to reactions about intact eggs, will facilitate studies employing defined antigens to ascertain those antigens which are most relevant to granuloma formation and modulation. Once these antigens are identified, the idiotypes or immunologic specificities of the reacting cell populations can be studied, and a more basic analysis of immunologic mechanisms will become feasible. In addition, the in vitro assay for the assessment of worm fecundity will be used for in vitro screening of anti-helminthic drugs and to study the interactions between worm fecundity and the host immune response to eggs. Since host morbidity is due to the adverse effects of the host/granulomatous response to the products of vitellogenesis, these studies will provide valuable information relative to the goal of reduced morbidity in schistosomiasis.